POS0137 FREQUENCIES OF WNT PATHWAY GENE VARIANTS ASSOCIATED WITH ANTI CARBAMYLATE PROTEIN IN EARLY RHEUMATOID ARTHRITIS
Authors: M. Acevedo-Godoy, S. J. Perdomo, W. Bautista-Molano, L. Chila, O. J. Calixto, J. M. Bello-Gualtero, C. Romero-Sánchez
Journal: Annals of the Rheumatic Diseases (2022)

Background Increased bone resorption and impaired bone formation characterize the pathogenesis of rheumatoid arthritis (RA). Wnt/β-catenin pathway regulates osteoblast function. Since bone mineral density (BMD) and RA joint destruction are partially inherited, we studied the association of Dickkopf-1 (DKK-1), sclerostin (SOST), Kremen-1 and lipoprotein receptor-related protein-5 (LRP-5) genes single nucleotide polymorphisms (SNPs). Objectives To establish the genotypic frequency of variants of the DKK-1 (rs1896368, rs1896367, rs1528873), SOST (rs6503475), Kremen-1 (rs132274) and LRP-5 (3736228) genes in patients with early RA (eRA) and first degree relative (FDR) with healthy controls (HC), and its association with autoimmunity profile. Methods Colombian individuals were matched by age and gender. Serological and clinical indices were measured. Variants associated with the Wnt pathway; DKK-1, SOST, LRP-5, and Kremen were analyzed using High Resolution Melting and confirmed by Sanger sequencing. A bivariate analysis was conducted in eRA and FDR. A logistic regression was performed. Results 232 individuals were evaluated; 66 eRA patients, 50 FDR, and 116 HC. For eRA, 78.8% were female, with a median age 52 years (IQR: 38,8-56). Higher levels of CRP: 4,2 (IQR: 1,6-11,6), RF: 30,2 (IQR: 1,2-74,1), anti-CCP: 7,81 (IQR: 7,81-104,9) and anti-Carbamylate protein (CarP): 17,7 (IQR: 12,3-31,8) were observed. Among eRA, FDR, and HC genotypic frequencies are listed in Table 1, there were significant differences among DKK-1 rs1528873 GA and AA (p&lt;001), Kremen GG and GA (p&lt;0,001), and LRP5 GG and GA (p=0,038), and GG with AA (p=0,023). In haplotype analysis between eRA and HC for DKK-1 rs1896368 GA and LRP-5 AA (p=0,033) and for LRP5 GG and AA DKK-1 rs1528873 (p&lt;0,001). Table 1. Population genotypic frequencies eRA FDR HC n(%) n(%) n(%) p value* DKK-1 rs1896367 27 (40,9) 25 (50) 57 (49,1) GG Native 39 (59,1) 25 (50) 59 (50,9) 0,528 GA Homozygous 4 (6,1) 4 (8) 8 (6,9) 0,890 AA Heterozygous 23 (34,8) 21 (42) 49 (42,2) 0,597 DKK-1 rs1896368 59 (89,4) 45 (90) 98 (84,5) GG Native 7 (10,6) 5 (10) 18 (15,5) 0,543 GA Homozygous 30 (45,5) 21 (42) 54 (46,6) 0,882 AA Heterozygous 29 (43,9) 24 (48) 44 (37,9) 0,450 DKK-1 rs1528873 25 (37,9) 24 (48) 59 (50,9) TT Native 42 (62,1) 26 (52) 57 (49,1) 0,233 TG Homozygous 24 (36,4) 5 (10) 6 (5,2) &lt;0,001 GG Heterozygous 1 (1,5) 19 (38) 53 (45,7) &lt;0,001 SOST rs6503475 51 (77,3) 35 (70) 85 (73,3) GG Native 15 (22,7) 15 (30) 31 (26,7) 0,657 GA Homozygous 13 (19,7) 9 (18) 28 (25) 0,580 AA Heterozygous 38 (57,6) 26 (52) 56 (48,3) 0,488 KREMEN rs132274 62 (93,9) 28 (56) 102 (87,9) CC Native 4 (6,1) 22 (44) 14 (12,1) &lt;0,001 CT Homozygous 35 (53) 6 (12) 54 (46,5) &lt;0,001 TT Heterozygous 27 (40,9) 22 (44) 48 (41,4) 0,953 LRP-5 rs3736228 23 (34,8) 16 (32) 22 (19) CC Native 43 (65,2) 34 (68) 94 (81) 0,038 CT Homozygous 3 (4,5) 10 (20) 3 (2,6) 0,038 TT Heterozygous 20 (30,3) 6 (12) 19 (16,4) 0,023 In eRA SOST rs6503475 was associated with anti-CarP (AOR 3,4 [95%IC 1,1-10,8] p=0,037). LRP-5 with former smoking (AOR 8,6 [95%IC 2,0-36,4] p=0,004). Additionally, in patients with a combination of at least three SNPs with a lower frequency of anti-Carp peptide (AOR 0,09 [95%IC 0,012-0,608], p=0,014), meanwhile a combination of at least five SNPs with a higher frequency of anti-Carp (AOR 4,7 [95%IC 1,27-17,1] p=0,020) were observed. There were no differences in FDR group. Conclusion Significant associations between Wnt pathway genes variants, haplotypes, and antibody profile could reinforce evidence to relation of high titters of anti-CarP with decreased BMD in eRA patients. Acknowledgements Hospital Militar Central - Universidad El Bosqu Disclosure of Interests None declared